Most people drugs are hydrophilic molecules with a molecular weight between 300 and 20,000 and such molecules are usually given by parenteral administration. In many cases, enteral administration of these peptides via the gastrointestinal tract is preferred. However, oral administration of peptides and proteins is often limited by their instability in the gastrointestinal environment and/or poor absorption from the gut. To promote the absorption of these drugs, we first discovered unsaturated fatty acids with absorption enhancing activities and less harmful properties to the gastrointestinal membranes in hydrolysates of natural oil. The mechanisms whereby the permeability of drugs was enhanced by the fatty acids are associated with the disorder in the membrane's interior and the interaction of these fatty acids with the polar head group of phospholipid. Furthermore, we suggested that a SH-related substance was involved in the permeability enhancing effect of these fatty acids. Secondly, we developed a lympho-targeting delivery system for bleomycin by the combined effects of an ion-pair complex with dextran sulfate (DS) and an absorption enhancer. We found a very high lymphatic concentration when administered bleomycin-DS together with the absorption enhancer. Its mechanism may be due to a molecular sieving in the blood-lymph barrier in the intestinal tissues. Finally, to improve the intestinal absorption of peptides, we synthesized novel lipophilic derivatives of peptides including TRH (thyrotropin releasing hormone), tetragastrin, enkephalin, calcitonin and insulin by a chemical modification with fatty acids, while maintaining their pharmacological activities. The stability and permeability of these peptides were improved by acylation with some fatty acids having appropriate carbon numbers. Thus, we have established the strategies for improving the delivery of peptide drugs by various approaches. In future, the combination use of these approaches will be expected to develop the delivery systems of these drugs for therapeutic treatment.